Rahul N. Khurana, MD: Phase 1 Results on Vamikibart for Uveitic Macular Edema

Recent data from the Phase 1 DOVETAIL trial provided promising initial findings on vamikibart, an anti-IL-6 monoclonal antibody, as a non-steroidal immunomodulatory treatment option for patients with uveitic macular edema (UME).

These data, presented at the 128th Annual American Academy of Ophthalmology (AAO) Meeting, showed a significant improvement in visual acuity and reduction in retinal thickness with vamikibart in patients with UME, offering rapid and sustained benefits without the need for steroid treatment.

“With vamikibart treatment, we saw a rapid increase in visual acuity as soon as the first injection and maintained over the first three treatments,” presenter Rahul N. Khurana, MD, chief executive officer and partner at Northern California Retina Vitreous Associates, told HCPLive. “In addition to an improvement in visual acuity, we saw concurrent improvement in structure or decreases in the retinal anatomy with the UME.”

UME is a chronic and challenging complication in patients with uveitis, which can lead to impaired vision and reduced quality of life. Current therapies, primarily steroids, can manage the condition but present significant side effects, such as intraocular pressure (IOP) elevation and cataract formation. Vamikibart was specifically engineered for intravitreal delivery, offering a novel mechanism of action by targeting IL-6 pathways, a cytokine integral to inflammatory and angiogenic processes.

According to DOVETAIL, vamikibart demonstrated promise in reducing macular edema and improving visual acuity with a favorable safety profile. In the trial, patients with UME received vamikibart 0.25 mg, 1 mg, or 2.5 mg, with 3 injections administered over the trial period.

Participants experienced notable gains in best-corrected visual acuity (BCVA) shortly after the first vamikibart dose, with an average improvement of ~10 letters. These benefits were sustained at Week 12, with approximately 25% to 33% of patients treated with vamikibart achieving ≥15 letter improvements.

Structural improvements in retinal thickness were identified as early as after the first injection, suggesting rapid efficacy in reducing retinal swelling. These benefits extended beyond the initial treatment phase, with sustained visual acuity and reduced retinal thickness during the observation period in several patient groups. Inflammation markers, including intraretinal and subretinal fluid levels, also notably improved, with vamikibart-treated patients achieving a 90-100% success rate in resolving fluid presence by Week 12.

Safety was encouraging, with only one serious adverse event reported and low occurrences of pressure elevations and cataract formation. Mild intraocular inflammation, noted in some cases, was attributed to uveitis rather than the drug itself.

Given the promising Phase 1 results, vamikibart is advancing to the global Phase 3 MEERKAT and SANDCAT trials evaluating 2 vamikibart doses (0.25 mg or 1 mg) or a sham control. By inhibiting IL-6 signaling, vamikibart could offer a targeted approach to reduce inflammation in UME, potentially serving as a long-term, steroid-sparing treatment option.

“Even though this is Phase 1 data, based on this very strong data, they have now initiated two global Phase 3 clinical trials, and we're very excited about those clinical trials because if those results can be replicated, we can hopefully have another treatment option for our patients,” Khurana told HCPLive.

Disclosures: Relevant disclosures for Khurana include Abbvie, Genentech, Regeneron, Roche, and others.

Reference

_{Khurana RN. DOVETAIL Phase 1 Results on Anti-IL6 Monoclonal Antibody for Uveitic Macular Edema. Presented at the American Academy of Ophthalmology (AAO) 2024 Meeting. Chicago, Illinois. October 18-21, 2024.}